crossing96/oncoscreening huggingface dataset:
Candida nivariensis: Identification strategy in mycological laboratories.	Candida nivariensis is a cryptic fungal species classified within the Candida glabrata complex. It was described for the first time in 2005 by the means of DNA sequencing. We report a rare case of C. nivariensis deep-seated infection occurring in a 77-year-old man hospitalized for cysto-prostatectomy. Phenotypic testing based on the direct examination and the macroscopic features of the in vitro culture initially suggested C. glabrata species, while MALDI-TOF mass spectrometry enables correct identification. The isolate was found resistant to fluconazole, like in almost 20% of the reported cases. Herein, we present our practical strategy to reliably characterize this rare cryptic species. To date, MALDI-TOF mass spectrometry-based analysis showed very good results for such a purpose.	bladder
Hospital-specific probability of cystectomy affects survival from muscle-invasive bladder cancer.	OBJECTIVES: Radical cystectomies (RCs) are increasingly centralized, but bladder cancer can be diagnosed in every hospital The aim of this study is to assess the variation between hospitals of diagnosis in a patient's chance to undergo a RC before and after the volume criteria for RCs, to identify factors associated with this variation and to assess its effect on survival. METHODS AND MATERIALS: Patients diagnosed with muscle-invasive bladder cancer (cT2-4a,N0/X,M0/X) without nodal or distant metastases between 2008 and 2016 were identified through the Netherlands Cancer Registry. Multilevel logistic regression analysis was used to investigate the hospital specific probability of undergoing a cystectomy. Cox proportional hazard regression analysis was used to assess the case-mix adjusted effect of hospital-specific probabilities on survival. RESULTS: Of the 9,215 included patients, 4,513 (49%) underwent a RC. The percentage of RCs varied between 7% and 83% by hospital of diagnosis before the introduction of the first volume criteria (i.e., 2008-2009; minimum of 10 RCs). This variation decreased slightly to 17%-77% after establishment of the second volume criteria (i.e., 2015-2016; minimum of 20 RCs). Age, cT-stage and comorbidity were inversely and socioeconomic status was positively associated with RC. Both being diagnosed in a community hospital and/or being diagnosed in a hospital fulfilling the RC volume criteria were associated with increased use of RC compared to academic hospitals and hospitals not fulfilling the volume criteria. For each 10% increase in the percentage of RC in the hospital of diagnosis, 2-year case-mix adjusted survival increased 4% (hazard ratio 0.96, 95% confidence interval 0.94-0.98). CONCLUSION: Probability of RC varied between hospitals of diagnosis and affected 2-year overall survival. Undergoing a RC was associated with age, cT-stage, socioeconomic status, type of hospital, and whether the hospital of diagnosis fulfilled the RC volume criteria. Future research is needed to identify patient, tumor, and hospital characteristics affecting utilization of curative treatment as this may benefit overall survival.	bladder
Continent diversion: five decades of developments and evolution.	OBJECTIVE: To provide a chronological overview of the evolution of continent urinary diversion (CUD) over the last 50 years and to highlight important milestones. METHODS: We performed an extensive literature review and analysed different forms of urinary diversion worldwide. After the evaluation of surgical techniques, we assessed the advantages and disadvantages of assorted CUD approaches based on published long-term follow-up data. RESULTS: A wide variety of surgical options for CUD is available and feasible to date, although consensus among urologists regarding the 'gold standard' is still lacking. Several forms of orthotopic bladder substitutes and continent cutaneous urinary reservoirs have been shown to provide excellent long-term results. CONCLUSION: The last 50 years of CUD have seen constant evolution and refinement of techniques, but the best surgical approach remains unclear and there is no 'one-size-fits-all' option, but rather tailor-made approaches are necessary to ensure patient satisfaction.	bladder
Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer.	BACKGROUND: This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours. METHODS: Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients). RESULTS: Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers. CONCLUSIONS: Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01058707.	bladder
A cost-utility analysis of atezolizumab in the second-line treatment of patients with metastatic bladder cancer.	BACKGROUND: Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (os) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mbc). However, given lessened adverse events (aes) and preserved quality of life (qol) with atezolizumab, there might still be investment value. To evaluate that potential value, we conducted a cost-utility analysis (cua) of atezolizumab compared with chemotherapy from the perspective of the Canadian health care payer. METHODS: A partitioned survival model was used to evaluate atezolizumab compared with chemotherapy over a lifetime horizon (5 years). The base-case analysis was conducted for the intention-to-treat (itt) population, with additional scenario analyses for subgroups by IMvigor-defined PD-L1 status. Health outcomes were evaluated through life-year gains and quality-adjusted life-years (qalys). Cost estimates in 2018 Canadian dollars for systemic treatment, aes, and end-of-life care were incorporated. The incremental cost-effectiveness ratio (icer) was used to compare treatment strategies. Parameter and model uncertainty were assessed through sensitivity and scenario analyses. Per Canadian guidelines, cost and effectiveness were discounted at 1.5%. RESULTS: For the itt population, the expected qalys for atezolizumab and chemotherapy were 0.75 and 0.56, with expected costs of $90,290 and $8,466 respectively. The resultant icer for atezolizumab compared with chemotherapy was $430,652 per qaly. Scenario analysis of patients with PD-L1 expression levels of 5% or greater led to a lower icer ($334,387 per qaly). Scenario analysis of observed compared with expected benefits demonstrated a higher icer, with a shorter time horizon ($928,950 per qaly). CONCLUSIONS: Despite lessened aes and preserved qol, atezolizumab is not considered cost-effective for the second-line treatment of mbc.	bladder
Preoperative chemotherapy in clinically node positive muscle invasive bladder cancer: Radiologic variables can predict response.	PURPOSE: To evaluate pathologic downstaging after radical cystectomy and pelvic lymph node dissection for clinically lymph node positive urothelial bladder cancer and to determine optimal preoperative imaging variables in predicting pathologic nodal status. METHODS: We identified all patients with clinically lymph node positive urothelial bladder cancer who underwent radical cystectomy and extended pelvic lymph node dissection with intent to cure at our institution. Patients were stratified based on pathologic node status to determine clinical associations and survival outcomes. Pre and post-chemotherapy CT scans were reviewed to characterize lymph node size and morphology. We also sought to determine associations between post-chemotherapy radiology variables and pathologic response. RESULTS: We identified 130 patients with clinically node positive bladder cancer, out of which 76 (58.5%) received induction chemotherapy. Thirty three (43.4%) had pathologic T downstaging following chemotherapy, compared to 7 (12.9%) patients who had surgery alone (P< 0.0001). A complete nodal response (pN0) occurred in 31 (40.8%) patients post-chemotherapy, while 6 (11.1%) of those who received cystectomy alone ended up being pN0 (P< 0.0001). Median overall survival and recurrence-free survival were shorter in patients with pN+ versus pN0 disease (1.9 years vs. 12.8 years, P= 0.016 and 1.2 years vs. 4.3 years, P= 0.013, respectively). Review of 29 post chemotherapy CT scans showed that patients with pathologic nodal involvement had a greater median number of enlarged nodes (3.5 vs. 1, P= 0.038) and a greater median size of largest node (8.5 mm vs. 6.0 mm, P= 0.021) on imaging compared to those with complete pN0. Each 1 mm increase in size of the largest node on post-chemotherapy CT scan increased the chance of having pN+ disease by 1.57 (95% CI 1.02-2.44, P= 0.043). Using a median node size of 8 mm as a cut-off to predict pN+ disease provided a sensitivity and specificity of 72% and 80%, respectively (c-index = 0.761, P= 0.014). The positive predictive value for this cut-off was 87% (95% CI 58%-98%) and negative predictive value was 62% (32%-85%). CONCLUSION: Patients with clinically node positive bladder cancer may have significant pN0 after induction chemotherapy. Our data suggest a post-chemotherapy CT scan with an 8 mm nodal size cut-off may be a better predictor of pathologic nodal status than more traditional measures.	bladder
Gender discrepancies in bladder cancer: potential explanations.	INTRODUCTION: Gender differences in urothelial carcinoma of the bladder (UCB) exist. Although men have a higher incidence of UCB, women tend to have poorer outcomes. We have explored and summarized the evidence for gender differences of UCB diagnosis and prognosis, together with reasons for these disparities. AREAS COVERED: The incidence of UCB is 3-4 times higher in men than women. However, women are more likely to be diagnosed with advanced disease. Women have a higher stage-for-stage mortality compared to men, and their greatest risk of death appears to be within the first 2 years of diagnosis. Survival outcomes following radical cystectomy (RC) and radiotherapy are also poorer in women. Delays in diagnosis, differences in female anatomy, as well as poorer surgical outcomes post-RC appear to contribute significantly to the disparities noted between genders. Other factors such as exposure to risk factors, differential hormone signaling, and carcinogen breakdown may also have a role. EXPERT OPINION: The gender divide in UCB outcomes has to be addressed. Improved medical and patient education and centralization of RC are recommended.	bladder
[Single, immediate postoperative intra-vesical instillation (SI) compared to a single preoperative intra-vesical instillation of mitomycin C in non-muscle invasive bladder cancer (NMIBC). Phase II randomized trial].	OBJECTIVE: A single immediate instillation of mitomycin C is recommended after a complete transurethral resection of the bladder (TURB) in low- and intermediate-risk patients with NMIBC. Actually, post-TURB instillation is seldom used due to logistical difficulties and surgical contraindications. Our aim was to compare patients with single pre-TURB intra-vesical instillation and patients with a single, immediate post-TURB intra-vesical instillation of mitomycin C. METHODS: We performed a multicenter randomized trial between February 17, 2014 and November 24, 2016 (registration number 2012-004341-32). Sixty patients with two or less, primary or recurrent papillary bladder tumors and a negative urinary cytology were planned. Cystoscopy was performed at 3, 6 and 12 months after TURB. Our primary endpoint was disease-free interval. Secondary endpoints were recurrence rate at 3 and 12 months, rate of patients in whom instillation could not be performed and tolerance 1 month after TURB using BCI-Fr score. RESULTS: Among 35 eligible participants, 20 were randomly assigned in the pre-TURB instillation group and 15 in the post-TURB instillation group. Follow-up was comparable: 12,3±1,6 months in the SI group and 10,2±4,5 months in the pre-TURB instillation group. In the post-TURB instillation group, 2 patients didn't have any instillation. We did not identify significant differences in disease-free interval. Tolerance at 1 month after TURB was similar in both groups. CONCLUSION: Tolerance and efficacy were not significantly different. As expected, logisitics were easier for the health providers in the pre-TURB group where all patients had their instillation conversely to the post-TURB group. These results suggest that the advantages of a single immediate pre-TURB instillation warrant further evaluation of this strategy in a phase III randomized trial.	bladder
TFPI-2 inhibits the invasion and metastasis of bladder cancer cells.	INTRODUCTION: Bladder cancer metastasis seriously affects the prognosis of patients, but its molecular mechanism is unclear. This study sought to explore the roles of tissue factor pathway inhibitor-2 (TFPI-2) gene overexpression in the infiltration and metastasis of bladder cancer. MATERIALS: Firstly, real-time PCR and immunohistochemistry were used to compare the mRNA and protein expression levels, respectively, of TFPI-2 and matrix metalloproteinase-1 (MMP-1) in adjacent non-tumoral tissues, muscle-invasive bladder cancer (MIBC) tissues, and non-muscle-invasive bladder cancer (NMIBC) tissues. BIU-87-TFPI-2 cells that stably expressed TFPI-2 were generated by transfection with pcDNA3.1-TFPI-2. Real-time PCR and western blotting were performed to determine the mRNA and protein expression levels, respectively, of TFPI-2 and MMP-1 in BIU-87-TFPI-2 cells. The invasion and migration abilities of BIU-87-TFPI-2 cells were investigated using the Transwell chamber method. RESULTS: TFPI-2 was found to be significantly downregulated in bladder cancer tissue. The expression of MMP-1 was increased with the progression of bladder cancer. BIU-87 cells that overexpressed TFPI-2 were successfully generated by transfection with pcDNA3.1-TFPI-2. TFPI-2 overexpression in BIU-87 cells significantly inhibited cancer cell invasion and metastasis. Furthermore, the mRNA and protein expression levels of MMP-1 were significantly reduced in TFPI-2-overexpressing cells. CONCLUSION: Decreased TFPI-2 expression in bladder tissue was correlated with invasion and metastasis in bladder cancer. TFPI-2 overexpression could inhibit bladder cancer cell invasion and migration in vitro by inhibiting MMP-1 protein expression. LEVEL OF PROOF: 3.	bladder
Development of an Immune-Related Risk Signature in Patients with Bladder Urothelial Carcinoma.	With recent advances in immunooncology and tumor microenvironment, the treatment landscape of bladder urothelial carcinoma has been changing dramatically. We aim to construct an immune gene-related signature which can predict BLCA patients' overall survival. Transcriptomic data of BLCA patients was downloaded from The Cancer Genome Atlas database, and immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Prognostic immune-related genes were identified. We then constructed and validated an immune gene-related signature. Tumor-related transcription factors were downloaded from the Cistrome database, and a network between them and prognostic immune-related genes was generated. Cox's proportional hazards model and the Kaplan-Meier survival analysis were performed to assess our signature's prognostic ability. Relationship between the signature and patients' clinicopathologic features was then explored to validate its clinical value. We further downloaded concentration of six types of immune cells from the Tumor Immune Estimation Resource database to explore immune-related potential mechanisms of the signature.	bladder
Reduction of Bladder Volume after BCG Immunotherapy.	Bacillus Calmette-Guérin (BCG) immunotherapy is the most effective treatment for carcinoma in situ and high-risk non-muscle invasive bladder cancer (NMIBC). However, it can also provoke diverse side effects. We found 1 patient with a significantly and rapidly reduced bladder volume after the instillation of BCG. Few such cases and corresponding treatments have been reported. We speculated that the tuberculosis infection existed, so antitubercular therapy was given. After a 3-month oral intake of rifampicin, isoniazid, and ofloxacin, the volume of bladder returned to normal and the voiding symptoms disappeared. This case indicated that the reduction of bladder volume caused by BCG instillation could be treated with antitubercular therapy. Prompt and accurate diagnosis was important for the management.	bladder
Gamma/Delta T-Cells Enhance Carboplatin-induced Cytotoxicity Towards Advanced Bladder Cancer Cells.	BACKGROUND/AIM: Bladder cancer (BLCA, urothelial bladder cancer) is one of the most common malignancies with increasing incidence and mortality worldwide. Poor diagnosis and the limitation of treatment is still an unmet need in clinical practice. γδ T-Cells have been paid increasing attention because of their potent cytotoxicity against tumors. Herein, we investigated the cytolytic effect of γδ T-cells in combination with the chemotherapeutic drug, carboplatin, against BLCA cells. MATERIALS AND METHODS: The standard protocol for the induction and expansion of peripheral blood mononuclear cell-derived γδ T-cells was a zoledronic acid/interleukin-2-based medium system for 2 weeks. The cytotoxicity of γδ T-cells with and without carboplatin against BLCA cells was examined. RESULTS: After incubation, T-cell receptor-positive γδ T-cells showed a natural killer cell-like phenotypic characteristic and dose-dependently increased cytotoxicity against BLCA cells. Interestingly, we found that in advanced BLCA cells, which were more resistant to carboplatin, the cell viability was significantly (p<0.05) reduced in the presence of γδ T-cells. CONCLUSION: Our findings showed that γδ T-cell therapy has potent benefit in cancer treatment.	bladder
Relationship between post-void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma.	OBJECTIVES: To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. METHODS: The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. RESULTS: The median follow-up period for all patients was 44 months. The presence of residual urine (P = 0.0164) and pyuria (P = 0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P = 0.0002) and intermediate-risk groups (P = 0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P = 0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guérin treatment. CONCLUSIONS: Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.	bladder
16-Hydroxycleroda-3,13-dien-15,16-olide Induces Apoptosis in Human Bladder Cancer Cells through Cell Cycle Arrest, Mitochondria ROS Overproduction, and Inactivation of EGFR-Related Signalling Pathways.	A clerodane diterpene compound 16-hydroxycleroda-3,13-dien-15,16-olide (CD) is considered a therapeutic agent with pharmacological activities. The present study investigated the mechanisms of CD-induced apoptosis in T24 human bladder cancer cells. CD inhibited cell proliferation in a concentration and time-dependent manner. CD-induced overproduction of reactive oxygen species and reduced mitochondrial membrane potential, associated with reduced expression of Bcl-2 and increased levels of cytosolic cytochrome c, cleaved PARP-1 and caspase-3. In addition, CD treatment led to cell cycle arrest at the G0/G1 phase and inhibited expression of cyclin D1 and cyclin-dependent kinases 2 and 4 and led to increased levels of p21, p27Kip1 and p53. All of these events were accompanied with a reduction of pEGFR, pMEK1/2, pERK1/2, pAkt, pmTOR, pP70S6K1, HIF-1α, c-Myc and VEGF. RNAseq-based analysis revealed that CD-induced cell death was characterised by an increased expression of stress and apoptotic-related genes as well as inhibition of the cell cycle-related genes. In summary, CD induces apoptosis in T24 bladder cancer cells through targeting multiple intracellular signaling pathways as a result of oxidative stress and cell cycle arrest.	bladder
Research on mechanism of miR-130a in regulating autophagy of bladder cancer cells through CYLD.	PURPOSE: The study aimed to explore the regulatory mechanism of micro ribonucleic acid (miR)-130a in the autophagy of bladder cancer cells through cylindromatosis (CYLD). METHODS: Human bladder cancer T24 cell line was used as the objects of the study. After miR-130a was knocked down using small-interfering RNA (siRNA) in T24 cell line, the changes in expressions of miR-130a and CYLD in each group were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The cell proliferation in each group was detected using cell counting kit-8 (CCK8) assay and flow cytometry. The changes in mRNA and protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 were determined using qRT-PCR and Western blotting. The autolysosomes were detected through acridine orange (AO)/ethidium staining bromide (ER) staining. Moreover, CYLD was knocked down using siRNA, and then the changes in mRNA expressions of miR-130a, LC3 and Beclin1 in each group were detected through qRT-PCR. RESULTS: After interference in miR-130a with siRNA, miR-130a-siRNA group had a significantly lower mRNA expression of miR-130a compared with NC-siRNA group and a significantly higher mRNA expression of CYLD (p<0.05), obviously inhibited cell proliferation (p<0.05), and decreased significantly mRNA and protein expressions of LC3 showing Beclin1 (p<0.05), and an evidently smaller number of autolysosomes. After knockdown of CYLD using siRNA, the mRNA expression of miR-130a had no significant changes (p>0.05), while the mRNA expressions of LC3 and Beclin1 declined significantly in CYLD-siRNA group compared with those in NC-siRNA group (p<0.05). CONCLUSION: MiR-130 can promote the autophagy of bladder cancer cells through regulating CYLD, thus facilitating the proliferation of tumor cells.	bladder